RDoC
Research Domain Criteria
RDoC: Research Domain Criteria Initiative
Project typeResearch framework
SponsorsNational Institute of Mental Health
Project coordinatorBruce Cuthbert[1]
DurationJanuary 28, 2010 (2010-01-28)[2]
WebsiteNIMH.NIH.gov/Research-priorities/rdoc

The Research Domain Criteria (RDoC) project is an initiative of personalized medicine in psychiatry developed by US National Institute of Mental Health (NIMH). In contrast to the Diagnostic and Statistical Manual of Mental Disorders (DSM) maintained by the American Psychiatric Association (APA), RDoC aims to address the heterogeneity in the current nosology by providing a biologically-based, rather than symptom-based, framework for understanding mental disorders.[3] "RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness."[4]

Call for creation

The National Institute of Mental Health oversees the RDoC initiative.

The 2008 NIMH Strategic Plan calls for NIMH to "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures."[5] The strategic plan continues:

Currently, the diagnosis of mental disorders is based on clinical observation—identifying symptoms that tend to cluster together, determining when the symptoms appear, and determining whether the symptoms resolve, recur, or become chronic. However, the way that mental disorders are defined in the present diagnostic system does not incorporate current information from integrative neuroscience research, and thus is not optimal for making scientific gains through neuroscience approaches. It is difficult to deconstruct clusters of complex behaviors and attempt to link these to underlying neurobiological systems. Many mental disorders may be considered as falling along multiple dimensions (e.g., cognition, mood, social interactions), with traits that exist on a continuum ranging from normal to extreme. Co-occurrence of multiple mental disorders might reflect different patterns of symptoms that result from shared risk factors and perhaps the same underlying disease processes.

To clarify the underlying causes of mental disorders, it will be necessary to define, measure, and link basic biological and behavioral components of normal and abnormal functioning. This effort will require integration of genetic, neuroscience, imaging, behavioral, and clinical studies. By linking basic biological and behavioral components, it will become possible to construct valid, reliable phenotypes (measurable traits or characteristics) for mental disorders. This will help us elucidate the causes of the disorder, while clarifying the boundaries and overlap between mental disorders. In order to understand mental disorders in terms of dimensions and/or components of neurobiology and behaviors, it will be important to:

  • Initiate a process for bringing together experts in clinical and basic sciences to jointly identify the fundamental behavioral components that may span multiple disorders (e.g., executive functioning, affect regulation, person perception) and that are more amenable to neuroscience approaches.
  • Develop reliable and valid measures of these fundamental components of mental disorders for use in basic studies and in more clinical settings.
  • Determine the full range of variation, from normal to abnormal, among the fundamental components to improve understanding of what is typical versus pathological.
  • Integrate the fundamental genetic, neurobiological, behavioral, environmental, and experiential components that comprise these mental disorders.[5]

Contrast with DSM

On April 29, 2013, a few weeks before the publication of the DSM-5, NIMH director Thomas Insel published a blog post critical of the DSM methodology and highlighting the improvement offered by the RDoC project.[6]

Wrote Insel:

While DSM has been described as a 'Bible' for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been "reliability" – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure.[6]

In that post, Insel wrote: "Patients with mental disorders deserve better."[6] He would later elaborate on this point, saying "I look at the data and I'm concerned. ... I don't see a reduction in the rate of suicide or prevalence of mental illness or any measure of morbidity. I see it in other areas of medicine and I don't see it for mental illness. That was the basis for my comment that people with mental illness deserve better."[7]

In their effort to resolve their issues with the new DSM, the NIMH launched the Research Domain Criteria Project (RDoC), based on four assumptions:

  • A diagnostic approach based on the biology as well as the symptoms must not be constrained by the current DSM categories,
  • Mental disorders are biological disorders involving brain circuits that implicate specific domains of cognition, emotion, or behavior,
  • Each level of analysis needs to be understood across a dimension of function,
  • Mapping the cognitive, circuit, and genetic aspects of mental disorders will yield new and better targets for treatment.[6]

Insel stressed that the RDoC is not designed as diagnostic criteria to replace the DSM, but rather as a research framework, for future development. His argument centers around the claim that, "symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment."[6] As a result of this position, the NIMH is no longer using the DSM as the criteria upon which they will evaluate funding of future clinic trials.[6]

DSM researcher Eric Hollander was quoted as saying "I do think it does represent a lack of interest and faith on behalf of NIMH for the DSM process and an investment in alternative diagnostic systems."[7]

A NIMH description of RDoC explained:

Currently, diagnosis in mental disorders is based on clinical observation and patients' phenomenological symptom reports ... However, in antedating contemporary neuroscience research, the current diagnostic system is not informed by recent breakthroughs in genetics; and molecular, cellular and systems neuroscience.[8]

RDoC matrix

The RDoC matrix is one way of organizing the concepts involved, with domains as tables, constructs as rows, sub-constructs as subrows and units of analysis often presented as columns.

Negative Valence Systems, as of January 2022[9]
Construct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Acute Threat (Fear)
  • Fear survey schedule
  • SUDS
  • Behavioral approach test
  • CO2 challenge test
  • Cold pressor test
  • Fear conditioning
  • Stranger tests
  • Trier social stress test
Potential Threat (Anxiety)
n/a
  • Anxiety Sensitivity Index
  • BIS
  • Fear of Negative Evaluation Scale
  • Intolerance of Uncertainty Scale
  • LEDS
  • NPU Threat Task
Sustained Threat
  • Dysregulated HPA axis
  • Error-related negativity
  • Childhood Trauma Questionnaire
  • LEDS
  • Risky Families
  • STRAIN
  • TESI
  • Youth Life Stress Interview
n/a
Loss n/a
  • Sadness eliciting film clips
Frustrative Nonreward n/a n/a
  • Frustrative Nonreward Responsiveness Subscale
  • Questionnaire of Daily Frustrations
  • Lab-TAB
  • PSAP
Positive Valence Systems, as of January 2022[9]
Construct / Subconstruct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Reward Responsiveness Reward Anticipation n/a n/a n/a n/a n/a n/a
  • Monetary incentive delay
Initial Response to Reward
  • CREB
  • Endocannabinoids
  • FosB
  • Glutamate
  • Mu and delta opioid
  • Orexin
n/a
  • Anterior Ins
  • Dorsal ACC
  • LH
  • Medial OFC
  • Nucleus accumbens
  • Ventral pallidum
  • Ventromedial PFC
  • VTA
n/a
  • Taste reactivity
  • Consummatory subscale of TEPS
  • PANAS (state version)
  • Simple guessing task
Reward Satiation n/a n/a n/a n/a n/a n/a
  • Fixed-ratio satiation schedule
Reward Learning Probabilistic and Reinforcement Learning n/a n/a n/a n/a n/a n/a
Reward Prediction Error n/a
  • Goal tracking
  • Pavlovian approach
  • Reward-related speeding
  • Sign tracking
  • Affective forecasting
  • ASAM scale
  • Eating Expectancy Inventory
  • Generalized reward and punishment expectancy scale
  • Self-report of craving
  • TEPS anticipatory scale
  • Drifting Double Bandit
  • Rutledge Passive Lottery Task
Habit - PVS Elements (Correlates)
Reward Valuation Reward (probability)
Delay
Effort
Cognitive Systems, as of January 2022[9]
Construct / Subconstruct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Attention
  • Implementation
  • Control
  • Balance between TPN vs DMN
  • Implementation
    • local circuit interactions
    • pulvinar
    • TRN
  • Control
    • Amg
    • Ascending / descending information pathways
  • Attentional systems
  • fMRI
    • Sensory areas from peripheral to central
  • Auditory ERP
    • N1
    • N2
    • Neural oscillations
    • P1
    • P300
    • Processing negativity
  • Visual ERP
    • N2pc
    • Negativity (SN)
    • Neural oscillations
    • P300
    • Selection modulations of sensory ERP components
    • Slow waves
  • Peripheral physiology
    • Heart rate deceleration
    • Pupil dilation
Perception Visual
  • Subcortical
  • Cortical
  • Non-retinogeniculate
  • Local circuitry
    • Lateral interactions
    • Top-down interactions
  • Implicated in contextual and association fields (responsible for the influence of spatial context on target processing)
  • Perceptual anomalies of schizophrenia and depression
  • Scheme 1: Stages of Vision
    • Early Vision
      • Local computations
      • Retinotopic representations
    • Intermediate Vision
      • Nonlocal properties of images
      • Transformations beyond retinotopic representations
    • Late Vision
      • Representations of external objects
  • Scheme 2: Commonly Used Research Paradigms
    • Backward masking
    • Biological motion processing
    • Bistability
    • Coherent motion
    • Contour integration/interpolation
    • Contrast sensitivity
    • Cross modality paradigms
    • Emotion expression identification
    • Face identification
    • Figure ground
    • Lateral facilitation
    • Multistability
    • Object perception
    • Object recognition/perceptual closure/perceptual organization
    • Parallel/serial search
    • Reading
    • Vernier discrimination
    • Visual illusion susceptibility
  • Other Schemes
    • Action-Perception loops
    • Re-entrant processing
Auditory Elements (Correlates)
Olfactory / Somatosensory / Multimodal n/a n/a n/a n/a n/a n/a
  • Manipulation of ISI and/or intensity
  • Smell identification
Declarative Memory Elements (Correlates)
Language
Cognitive Control 1 of 2: Goal Selection; Updating, Representation, and Maintenance
2 of 2: Goal Selection; Updating, Representation, and Maintenance
1 of 2: Response Selection; Inhibition / Suppression
2 of 2: Response Selection; Inhibition / Suppression
Performance Monitoring
Working Memory Active Maintenance
Flexible Updating
Limited Capacity
Interference Control
  • Calbindin
  • Calretinin
  • Distinct types of inhibitory neurons
  • Parvalbumin
  • DLPFC
  • PFC-parietal-cingulate-dorsal Th-dorsal striatum
n/a n/a
  • Complex Span tasks
  • Delayed match to non-sample
  • Delayed match to sample
  • Keep track task
  • Letter memory/running memory
  • Letter number sequencing
  • n-back
  • Self-Ordered Pointing
  • Simple Span Tasks
  • Sternberg Item Recognition
Social Processes, as of January 2022[9]
Construct / Subconstruct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Affiliation and Attachment Elements (Correlates)
Social Communication Reception of Facial Communication
Production of Facial Communication
Reception of Non-Facial Communication
Production of Non-Facial Communication
Perception and Understanding of Self Agency
Self-Knowledge
Perception and Understanding of Others Animacy Perception
Action Perception
Understanding Mental States
Arousal and Regulatory Systems, as of January 2022[9]
Construct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Arousal
  • ADACL
  • POMS arousal subscale
  • Self-assessment mannequin
Circadian Rhythms
Sleep-Wakefulness
  • Intermediate/admixed sleep-wake states
  • Rest-activity patterns
  • Sensory arousal threshold
  • Sleep
  • Sleep-dependent neurobehavioral functions
  • Wakefulness
  • Finger tapping motor sequence task
  • Latency to persistent sleep
  • Multiple sleep latency testing
  • Non-REM sleep EEG slow wave activity
  • Sleep spindle
  • Total sleep time
  • Wake time after sleep onset
Sensorimotor Systems, as of January 2022[9]
Construct / Subconstruct Molecules Cells Neural Circuits Physiology Behavior Self-reports Paradigms
Motor Action Action Planning and Selection n/a n/a n/a
n/a
  • Go-before-you-know
Sensorimotor Dynamics n/a
  • Short afferent inhibition
n/a
  • Sensory Motor Adaptation Tasks
Initiation n/a n/a
n/a
  • Apathy
  • Catatonic stupor
  • Negative symptoms
  • Psychomotor retardation
  • Stuttering
  • Lille Apathy Rating Scale
  • Libet's Temporal Judgement
Execution n/a
  • Efferent and afferent spinal and peripheral pathways
  • Motor cortex
n/a
  • Motor evoked potential latency
Inhibition and Termination
  • Intracortical inhibitory interneurons
  • Striatal interneurons
n/a
Agency and Ownership n/a
n/a n/a
Habit - Sensorimotor n/a
  • PtA
  • Sensorimotor-BG
n/a
  • 2-step task
Innate Motor Patterns n/a n/a
n/a n/a

The domains are tentative: "It is important to emphasize that these particular domains and constructs are simply starting points that are not definitive or set in concrete."[8] Also, subconstructs have been added to some constructs. For example, Visual Perception, Auditory Perception, and Olfactory/Somatosensory/Multimodal perception as subconstructs of the Perception construct.[9]

Methodology

The RDoC methodology distinguishes itself from traditional systems of diagnostic criteria.

Unlike conventional diagnostic systems (e.g. DSM) which use categorization, RDoC is a "dimensional system" — it relies on dimensions that "span the range from normal to abnormal."[8]

Whereas conventional diagnostic systems incrementally revise and build upon their pre-existing paradigms, "RDoC is agnostic about current disorder categories."[8] Official documents explain this feature, writing: "Rather than starting with an illness definition and seeking its neurobiological underpinnings, RDoC begins with current understandings of behavior-brain relationships and links them to clinical phenomena."[8]

Unlike conventional diagnostic systems, which typically rely on self-report and behavioral measures alone, the RDoC framework has the "explicit goal" of allowing investigators access to a wider range of data. In addition to self-report measures or measure of behavior, RDoC also incorporates units of analysis beyond those found in the DSM — allowing RDoC to be informed by insights into genes, molecules, cells, circuits, physiology, and large-scale paradigms.[8] Early data driven approaches to RDoC based continuous transdiagnostic psychiatric phenotypes predict clinical prognosis across diagnosis and have genetic correlates that in not only clinical populations.[10][11]

References

  1. "RDoC Unit and Work Group Members". National Institute of Mental Health. Archived from the original on 31 October 2016. Retrieved 31 October 2016.
  2. Asher, Jules (28 January 2010). "Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research". National Institute of Mental Health.
  3. Cuthbert, Bruce N; Insel, Thomas R (Dec 2013). "Toward the future of psychiatric diagnosis: the seven pillars of RDoC". BMC Medicine. 11 (1): 126. doi:10.1186/1741-7015-11-126. ISSN 1741-7015. PMC 3653747. PMID 23672542.
  4. Insel, Thomas R.; Lieberman, Jeffrey A. (13 May 2013). "DSM-5 and RDoC: Shared Interests" (Press release). National Institute of Mental Health.
  5. 1 2 "The National Institute of Mental Health Strategic Plan". National Institute of Mental Health. 6 November 2008. Strategy 1.4. Archived from the original on 17 December 2008.
  6. 1 2 3 4 5 6 Insel, Thomas (29 April 2013). "Director's Blog: Transforming Diagnosis". National Institute of Mental Health.
  7. 1 2 Szalavitz, Maia (7 May 2013). "Mental Health Researchers Reject Psychiatry's New Diagnostic 'Bible'". TIME.
  8. 1 2 3 4 5 6 "Research Domain Criteria (RDoC)". National Institute of Mental Health. 29 May 2013. Archived from the original on 1 June 2013.
  9. 1 2 3 4 5 6 7 "RDoC Matrix". National Institute of Mental Health. Archived from the original on 2022-01-21. Retrieved 16 January 2022.
  10. McCoy, Thomas H.; Yu, Sheng; Hart, Kamber L.; Castro, Victor M.; Brown, Hannah E.; Rosenquist, James N.; Doyle, Alysa E.; Vuijk, Pieter J.; Cai, Tianxi (2018-06-15). "High Throughput Phenotyping for Dimensional Psychopathology in Electronic Health Records". Biological Psychiatry. 83 (12): 997–1004. doi:10.1016/j.biopsych.2018.01.011. ISSN 1873-2402. PMC 5972065. PMID 29496195.
  11. McCoy, Thomas H.; Castro, Victor M.; Hart, Kamber L.; Pellegrini, Amelia M.; Yu, Sheng; Cai, Tianxi; Perlis, Roy H. (2018-06-15). "Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records". Biological Psychiatry. 83 (12): 1005–1011. doi:10.1016/j.biopsych.2017.12.004. ISSN 1873-2402. PMC 5972060. PMID 29496196.

Further reading

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